OZONE-INDUCED AIRWAY HYPERRESPONSIVENESS AND LOSS OF NEURONAL M(2) MUSCARINIC RECEPTOR FUNCTION

The effect of acute ozone exposure on the function of efferent parasympathetic nerves, M(3) muscarinic receptors on airway smooth muscle, and inhibitory M(2) muscarinic receptors on the parasympathetic nerves was studied. Immediately after exposure to 2.0 ppm ozone for 4 h, guinea pigs became hyperresponsive to electrical stimulation of the vagus nerves. The normal airway response to intravenous cholinergic agonists at this time demonstrates normal M(3) receptor function. M(2) muscarinic receptors on the nerves, which normally inhibit release of acetylcholine, were dysfunctional after ozone exposure, as demonstrated by the failure of the muscarinic agonist pilocarpine to inhibit, and the failure of the M(2) antagonist gallamine to potentiate, vagally mediated bronchoconstriction. Thus, loss of inhibitory M(2) muscarinic receptor function after ozone exposure potentiates release of acetylcholine from the vagus nerves, increasing vagally mediated bronchoconstriction. By 14 days, postozone responses to vagal nerve stimulation were not different from those of air-exposed animals and the function of the neuronal M(2) muscarinic receptor was normal, confirming that ozone-induced hyperresponsiveness is reversible.